Article
Chemistry, Multidisciplinary
Yang You, Jianpei Xu, Yipu Liu, Haichun Li, Laozhi Xie, Chuchu Ma, Yinzhe Sun, Shiqiang Tong, Kaifan Liang, Songlei Zhou, Fenfen Ma, Qingxiang Song, Wenze Xiao, Kaikai Fu, Chengxiang Dai, Suke Li, Jigang Lei, Qiyong Mei, Xiaoling Gao, Jun Chen
Summary: This study presents a platform architecture that combines apoptosis induction, drug loading, and functionalized proteome regulation to create an apoptotic vesicle delivery system for ischemic stroke treatment. Alpha-mangostin (alpha-M) was loaded onto mesenchymal stem cell (MSC)-derived apoptotic vesicles as an antioxidant and anti-inflammatory agent, and a targeting peptide was modified on the surface of the vesicles. The engineered apoptotic vesicles targeted the injured ischemic brain and showed enhanced neuroprotective activity. The protein payloads of the vesicles were found to regulate immunological response, angiogenesis, and cell proliferation, contributing to their therapeutic effects. These findings provide a universal framework for creating apoptotic vesicle-based therapeutic drug delivery systems and demonstrate the potential of MSC-derived apoptotic vesicles for treating neural injury.
Article
Engineering, Biomedical
Lina Qiu, Ying Cai, Yanqin Geng, Xiuhua Yao, Lanxing Wang, Hongmei Cao, Xuebin Zhang, Qiaoli Wu, Deling Kong, Dan Ding, Yang Shi, Yuebing Wang, Jialing Wu
Summary: This study found that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can pass through the disrupted blood-brain barrier and accumulate in injured brain regions of patients with ischemic stroke. The study also found that tPA can promote the homing of MSC-EVs to the ischemic brain and increase the uptake of MSC-EVs by astrocytes. Furthermore, MSC-EVs alleviate tPA-induced disruption of the blood-brain barrier and hemorrhage by inhibiting astrocyte activation and inflammation. The study provides a noninvasive method for real-time tracking of MSC-EVs in the ischemic brain after tPA treatment and highlights the potential of MSC-EVs as thrombolytic adjuvants for ischemic stroke.
ACTA BIOMATERIALIA
(2022)
Article
Neurosciences
A. D. Roseborough, Y. Zhu, L. Zhao, S. R. Laviolette, S. H. Pasternak, S. N. Whitehead
Summary: The brain's response to acute injury involves increased permeability of the blood-brain barrier (BBB) and increased inflammation in microglia, which can lead to poor cognitive outcomes and neurological disease. Fibrinogen, a serum protein, enters the brain through the damaged BBB and interacts with local cells in a harmful way. Microglia, in response to injury, demonstrate increased activity of the NLRP3 inflammasome and release more pro-inflammatory cytokines. This study investigates the interaction between fibrinogen, microglial NLRP3 signaling, and extracellular vesicles (EVs), which can propagate inflammatory signaling and be detected in the circulation following BBB disruption.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Pharmacology & Pharmacy
Waqas Ahmed, Muhammed Shibil Kuniyan, Aqil Mohammad Jawed, Lukui Chen
Summary: Extracellular vesicles (EVs) are a promising therapeutic modality for neurological conditions, facilitating intercellular communication among brain cells. Their potential to pass through the blood-brain barrier (BBB) makes them highly promising for stroke management. Compared to existing drug-delivery vehicles, EVs have several advantages including the ability to surpass natural barriers, target specific cells, and maintain stability within the circulatory system.
Article
Biotechnology & Applied Microbiology
Yiyang Li, Bowen Liu, Tingting Zhao, Xingping Quan, Yan Han, Yaxin Cheng, Yanling Chen, Xu Shen, Ying Zheng, Yonghua Zhao
Summary: This study compared the protective efficacy of bone marrow mesenchymal stem cells derived extracellular vesicles (BMSC-EVs) and brain endothelial cells derived extracellular vesicles (BEC-EVs) on blood-brain barrier (BBB) integrity after acute ischemic stroke (IS). The findings indicated that both types of EVs had similar protective effects on reducing cerebral infarction volume, BBB leakage, and enhancing the expression of tight junction proteins ZO-1 and Claudin-5. Furthermore, BMSC-EVs showed superior efficacy in suppressing Caveolin-1 and improving neurological function.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Clinical Neurology
Laurens Winkelmeier, Tobias D. Faizy, Gabriel Broocks, Lukas Meyer, Christian Heitkamp, Caspar Brekenfeld, Christian Thaler, Paul Steffen, Maximilian Schell, Milani Deb-Chatterji, Uta Hanning, Helge Kniep, Mate E. Maros, Goetz Thomalla, Jens Fiehler, Fabian Alexander Flottmann
Summary: The clinical benefit of endovascular therapy in patients with large ischemic stroke is associated with the number of recanalization attempts. At least 2 recanalization attempts improve the likelihood of favorable functional outcomes, while more than 2 attempts should be carefully assessed.
Article
Endocrinology & Metabolism
Chao Li, Chunyang Wang, Yi Zhang, Owais K. Alsrouji, Alex B. Chebl, Guangliang Ding, Quan Jiang, Stephan A. Mayer, Mei Lu, Max K. Kole, Horia L. Marin, Li Zhang, Michael Chopp, Zheng Gang Zhang
Summary: The study demonstrates that small extracellular vesicles derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tissue plasminogen activator (tPA) have a positive effect on treating cerebral large vessel occlusion, reducing infarct volume, increasing recanalization, improving cerebral blood flow, and reducing blood-brain barrier leakage. This treatment also effectively suppresses a network of microRNAs and proteins that mediate thrombosis, coagulation, and inflammation.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Review
Clinical Neurology
Lei Hao, Yongtao Yang, Xiaoli Xu, Xiuming Guo, Qunling Zhan
Summary: Ischemic stroke is the most common type of stroke and the immune system plays a crucial role in its development. Microglia, the first responders in the central nervous system, can switch between pro- and anti-inflammatory states. Modulating microglia polarization towards an anti-inflammatory phenotype could be a potential treatment for ischemic stroke. This review explores the impact of mesenchymal stem cells and their extracellular vesicles on microglia activation and phenotype polarization, providing evidence for novel therapeutics.
FRONTIERS IN NEUROLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Yi-Xuan Li, Hong-Bo Wang, Jian-Bo Jin, Chun-Lin Yang, Jing-Bo Hu, Jing Li
Summary: Ischemic stroke, a common cerebrovascular disease, often leads to disability and death. Nanoparticle delivery systems can traverse the blood-brain barrier (BBB) for drug transportation, using pathways such as passive diffusion, adsorption-mediated endocytosis, receptor-mediated transport, and carrier-mediated transport. Common materials used for brain-targeted delivery include natural polymers, synthetic polymers, inorganic materials, and phospholipids. This review introduces the applications of nano delivery systems in the treatment of ischemic stroke and proposes new ideas and prospects for designing feasible and effective nano delivery systems.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biology
Angelica Carandina, Chiara Favero, Roberto Maria Sacco, Mirjam Hoxha, Giuseppe Torgano, Nicola Montano, Valentina Bollati, Eleonora Tobaldini
Summary: This study found that specific subtypes of extracellular vesicles are associated with stroke severity and both short- and long-term outcomes. Extracellular vesicles could serve as a valid tool to improve risk stratification in patients with ischemic stroke and post-recanalization treatment monitoring.
Article
Clinical Neurology
Felix C. Ng, Leonid Churilov, Nawaf Yassi, Timothy J. Kleinig, Vincent Thijs, Teddy Y. Wu, Darshan G. Shah, Helen M. Dewey, Gagan Sharma, Patricia M. Desmond, Bernard Yan, Mark W. Parsons, Geoffrey A. Donnan, Stephen M. Davis, Peter J. Mitchell, Richard Leigh, Bruce C. Campbell
Summary: This study found that the severity of tissue injury within the infarct, as determined by assessing the integrity of the blood-brain barrier (BBB), is independently associated with improved functional outcome in patients with ischemic stroke. In addition to reducing infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.
Review
Neurosciences
Lu Cao, Yanbo Zhou, Mengguang Chen, Li Li, Wei Zhang
Summary: Pericytes are multipotent cells located on capillaries and play a crucial role in maintaining the blood-brain barrier and regulating the neurovascular system. Dysfunction of pericytes can lead to diseases such as stroke. Recent studies suggest that pericytes can be a therapeutic target for ischemic stroke.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Afsaneh Asgari Taei, Pariya Khodabakhsh, Sanaz Nasoohi, Maryam Farahmandfar, Leila Dargahi
Summary: It is well known that the therapeutic effects of transplanted mesenchymal stem cells (MSCs) in ischemic stroke are not due to cell replacement, but rather the secretion of bioactive molecules. The secretome of MSCs, which includes growth factors, cytokines, and extracellular vesicles, plays a crucial role in neuroprotection. The application of secretome derivatives, such as conditioned medium or purified extracellular vesicles, has shown significant advantages over MSC transplantation in stroke treatment.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Devika S. Manickam
Summary: The field of drug delivery has made significant advances in enhancing the potential of various types of drug candidates. Extracellular vesicles (EVs) are a promising class of natural, cell-derived carriers for drug delivery. Medium-to-large EVs can carry healthy and functional mitochondria, repair cellular damage, and have broad application prospects in the treatment of neurodegenerative diseases, cardiovascular diseases, and metabolic diseases.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Biotechnology & Applied Microbiology
Pengtao Li, Rui Yin, Yihao Chen, Jianbo Chang, Lang Yang, Xiaoyu Liu, Houshi Xu, Xiao Zhang, Shihua Wang, Qin Han, Junji Wei
Summary: This systematic review and meta-analysis evaluated the efficacy of engineered extracellular vesicles (EEVs) in treating ischemic stroke (IS) and compared them with natural extracellular vesicles (EVs). The results showed that EEVs were superior to natural EVs in reducing infarct volume, improving neurological scores, promoting behavioral recovery, reducing inflammatory factor release, and increasing neuron counts.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Neurosciences
Kasey L. Jackson, Hemangini A. Dhaibar, Robert D. Dayton, Sergio G. Cananzi, William G. Mayhan, Edward Glasscock, Ronald L. Klein
Article
Endocrinology & Metabolism
Sergio G. Cananzi, William G. Mayhan
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2019)
Article
Hematology
Denise M. Arrick, Shu Yang, Chun Li, Sergio Cananzi, William G. Mayhan
Article
Substance Abuse
Sergio G. Cananzi, William G. Mayhan
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2019)
Article
Clinical Neurology
Sergio Giuseppe Cananzi, Luke A. White, Mansoureh Barzegar, Christen J. Boyer, Oleg Y. Chernyshev, J. Winny Yun, R. E. Kelley, Isaac Almendros, Alireza Minagar, Ramon Farre, Jonathan Steven Alexander
Article
Multidisciplinary Sciences
Yunjia Zhang, Boxun Li, Sergio Cananzi, Chuanhui Han, Lei-Lei Wang, Yuhua Zou, Yang-Xin Fu, Gary C. Hon, Chun-Li Zhang
Summary: The study reveals that the transcription factor DLX2 can unlock the multipotentiality of adult astrocytes, allowing them to rapidly become neural progenitor cells and differentiate into neurons, astrocytes, and oligodendrocytes. Single-cell transcriptomics and pseudotime trajectories confirm the neural stem cell-like behavior of reprogrammed astrocytes. This discovery provides insights into potential neural regeneration strategies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
